The impact of TGFβ1 levels on pulmonary disease progression in cystic fibrosis patients

Background: Pulmonary involvement is the leading cause of mortality and morbidity in Cystic Fibrosis (CF). Early diagnosis and effective treatment of pulmonary exacerbations are essential to slow disease progression, preserve lung function and improve quality of life. Recent research suggests that Transforming Growth Factor β1 (TGFβ1) is an important gene that modulates phenotypic expression in CF and may be a critical mediator of lung injury. This study aims to investigate the utility of this cytokine as a potential biomarker for the diagnosis of exacerbations and evaluation of treatment response by examining serum and sputum TGFβ1 levels in CF patients. The feasibility of measuring TGFβ1 in sputum samples was also evaluated, especially to overcome the limitations of invasive methods and to increase patient comfort. The aim is to develop a practical and effective diagnostic and monitoring method that can be easily integrated into clinical practice. Methods: The study included 45 patients aged 0-23 years diagnosed with CF by sweat test and genetic analysis. Ten patients were excluded due to frequent recurrence of pulmonary exacerbations, failure to attend follow-up visits or long hospitalization, and the analysis was completed with 35 patients. Sociodemographic and clinical data, pulmonary function tests, and routine laboratory results were recorded. Serum and sputum samples were collected during exacerbations, after treatment, and during the symptom-free period. TGFβ1 levels in serum and sputum were measured quantitatively by ELISA, and its concentrations were calculated using a four-parameter logistic regression model. Statistical analyses of the study were performed using IBM SPSS Statistics for Windows, version 20.0. Results: The median age of the 35 pediatric CF patients included in the study was 15.0 years (min-max: 0.6-23.0), and the male/female ratio was 19/16. As a result of TGFβ1 measurements in serum and sputum samples, a statistically significant difference was found between the exacerbation period and the post-exacerbation period (p=0.002). In the post-exacerbation period, serum and sputum levels of TGFβ1, CRP and procalcitonin decreased, while FEV₁ increased compared to the exacerbation period. These changes were significant for all parameters except sputum TGFβ1 (p<0.001, p=0.544 for sputum TGFβ1). Differences between other time points were not statistically significant (p>0.05). Conclusion: This study evaluated the time-dependent changes in serum and sputum TGFβ1 levels in CF patients and the relationship of this cytokine to inflammatory processes and lung function. The results showed that serum and sputum TGFβ1 levels were significantly higher during the exacerbation period and showed a significant decrease after treatment. The parallel trends in serum and sputum TGFβ1 levels suggest that sputum TGFβ1 can be used as a non-invasive indicator of inflammation. In addition, correlations were observed between TGFβ1 changes and markers of inflammation such as CRP and procalcitonin, and lung function markers such as FEV1, but these correlations were not statistically significant. The results suggest that TGFβ1 may have a valuable contribution to clinical practice as a non-invasive biomarker that improves patient convenience in both monitoring inflammation and assessing treatment response. Keywords: Biomarkers, Cystic Fibrosis, Respiratory Tract Infections, Sputum, Transforming Growth Factor Beta1 (TGFβ1)